Organotypic cultures of central and peripheral neural tissues will be used in conjunction with muscle explants as model systems to suplement and analyze in situ studies in cellular neurophysiology and neuropathology. The unique geometry of these relatively two-dimensional cellular arrays in vitro will be exploited to facilitate close correlation of the bioelectric and cytologic properties of cultured neurons and muscle cells under a variety of experimental conditions, including systematic application of patterned electric stimuli as well as pharmacologic, immunologic and other physico-chemical agents. Since neural tissues from embryonic, fetal or neonatal mammals (including human) can adapt well to culture conditions, emphasis will be placed on functional studies during the development of these isolated groups of neural (and related) cells, utilizing both intact explants (Crain, Internat. Rev. Neurobiol. 9:1-43, 1966), as well as reaggregating CNS cells after complete enzymatic dissociation (Crain and Bornstein, Science 176:182-184, 1972). These model systems will permit more direct analyses of inductive, trophic or other chemical factors which may underly synaptogenesis and formation of organized cell assemblies, with patterned excitatory and inhibitory circuits. Experiments leading to "plastic" alterations of CNS tissues associated with functional shaping of these behavioral network models will also be carried out.